Inflammasome and Gasdermin Signaling Networks for Regulation of Pyroptosis and Cytokine Release
用于调节焦亡和细胞因子释放的炎性体和 Gasdermin 信号网络
基本信息
- 批准号:10654563
- 负责人:
- 金额:$ 188.67万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-07-24 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AcuteAlzheimer&aposs DiseaseAmyloidApoptosisApoptoticAutophagocytosisBiochemicalBiochemistryCASP1 geneCASP3 geneCASP8 geneCASP9 geneCaspaseCategoriesCell DeathCell LineageCell membraneCell physiologyCellsCellular biologyChaperone Protein InteractionChronicCompensationComplexCrohn&aposs diseaseCytolysisDNADiseaseDisease modelDissociationDysmyelopoietic SyndromesEffector CellElementsEpithelial CellsExtracellular SpaceFamilial Mediterranean FeverFunctional disorderGeneticGoalsGolgi ApparatusImmuneImmune responseImmunologicsInfectionInflammasomeInflammationInflammatoryInflammatory Bowel DiseasesInnate Immune ResponseInterleukin-1 betaInvestigationLinkLiteratureLyticMacrophageMediatingMediatorMembraneMolecularMultiple SclerosisMusMyeloid CellsMyocardial InfarctionN-terminalNecrosisNonlyticPathogenesisPathogenicityPathway interactionsPeptide HydrolasesPeptide Signal SequencesPopulationProductionProteinsPublishingReagentRegulationReportingSecretory VesiclesSignal TransductionSourceSterilityStimulusT-LymphocyteTestingTissuesUlcerative ColitisVDAC1 genecell killingcell typecytokineextracellulargastrointestinalgranulocytegut inflammationhuman diseaseintestinal epitheliummicrobialmouse modelneutrophilnovelprogramsresponserestraintstructural biologystructural determinantstrafficking
项目摘要
OVERALL PROGRAM PROJECT: ABSTRACT
Cell death pathways have historically been characterized by the proteases that become
activated during cell fate decisions. Apoptosis has been defined by initiator and effector caspase
activation and, largely due to the reagents available; cell death decisions were initially thought to
be binary – caspase-dependent (apoptosis) or caspase-independent (all others). Much like
other binary distinctions – like Th1 versus Th2 T cells or M1 versus M2 macrophages, which
have undergone substantial expansion in the past decade, cell death decisions and their
consequences are now recognized to be much more variables. In fact, even the mechanisms of
cell death have been refined. They are no longer categorized by the proteases which activate
the cascades but rather, by the effector mechanism. Necroptotic cell death is caused by
activation of the pore-forming protein, MLKL. Secondary necrosis is caused by activation of the
pore-forming protein, DFNA5 (Gasdermin E/GSDME), and pyroptosis is caused by activation of
the pore-forming protein, Gasdermin D (GSDMD) This last category of cell death - pyroptosis -
is one of the most immunologically important forms of cell death. Not only does pyroptosis kill
the cell, but also GSDMD activation allows the release of IL-1β. This cytokine is among the most
important in acute and chronic inflammation. Its secretion is implicated in rare genetic
inflammatory diseases such as Familial Mediterranean Fever as well as more common diseases
such as myocardial infarction, Alzheimer's disease, Crohn's disease and Ulcerative Colitis,
Multiple Sclerosis and many others. With the discovery of the inflammasome in 2002 and its
subsequent study, it became clear that the amyloid-like activation of these inflammasome
complexes drove pro-IL-1β cleavage and IL-1β release from the cell, but also pyroptosis.
Missing from this biochemistry, though, was the cell biology underlying IL-1β release. How is IL-
1β recognized by caspases and other proteases? If IL-1β is not released through a secretory
ER-Golgi mechanism, how is trafficked out of the cell? How is this release coordinated with
pyroptosis and other regulated cell death pathways that are operative in different populations of
immune effector cells. This Program Project aims to utilize cell physiology, biochemistry,
structural biology, and mouse and human disease models to unravel these important questions.
总体方案方案:摘要
项目成果
期刊论文数量(9)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The Ras GTPase-activating-like protein IQGAP1 bridges Gasdermin D to the ESCRT system to promote IL-1β release via exosomes.
- DOI:10.15252/embj.2022110780
- 发表时间:2023-01-04
- 期刊:
- 影响因子:11.4
- 作者:Liao, Yun;Chen, Xing;Miller-Little, William;Wang, Han;Willard, Belinda;Bulek, Katarzyna;Zhao, Junjie;Li, Xiaoxia
- 通讯作者:Li, Xiaoxia
The synthetic oleanane triterpenoid CDDO-2P-Im binds GRP78/BiP to induce unfolded protein response-mediated apoptosis in myeloma.
- DOI:10.1002/1878-0261.13447
- 发表时间:2023-12
- 期刊:
- 影响因子:6.6
- 作者:Luo, George;Aldridge, Kristin;Chen, Toby;Aslot, Vivek;Kim, Byung-Gyu;Han, Eun Hyang;Singh, Neelima;Li, Sai;Xiao, Tsan Sam;Sporn, Michael B.;Letterio, John J.
- 通讯作者:Letterio, John J.
Partners with a killer: Metabolic signaling promotes inflammatory cell death.
- DOI:10.1016/j.cell.2021.07.036
- 发表时间:2021-08-19
- 期刊:
- 影响因子:64.5
- 作者:Liu, Zhonghua;Xiao, Tsan Sam
- 通讯作者:Xiao, Tsan Sam
Mechanisms of Gasdermin Recognition by Proteases.
- DOI:10.1016/j.jmb.2021.167274
- 发表时间:2022-02-28
- 期刊:
- 影响因子:5.6
- 作者:Liu Z;Busscher BM;Storl-Desmond M;Xiao TS
- 通讯作者:Xiao TS
SARS-CoV-2 ORF3a-Mediated NF-κB Activation Is Not Dependent on TRAF-Binding Sequence.
- DOI:10.3390/v15112229
- 发表时间:2023-11-08
- 期刊:
- 影响因子:0
- 作者:Busscher BM;Befekadu HB;Liu Z;Xiao TS
- 通讯作者:Xiao TS
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
GEORGE R DUBYAK其他文献
GEORGE R DUBYAK的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('GEORGE R DUBYAK', 18)}}的其他基金
The role of Gasdermin E (DFNA5) in bacterial keratitis
Gasdermin E (DFNA5) 在细菌性角膜炎中的作用
- 批准号:
10196230 - 财政年份:2021
- 资助金额:
$ 188.67万 - 项目类别:
The role of Gasdermin E (DFNA5) in bacterial keratitis
Gasdermin E (DFNA5) 在细菌性角膜炎中的作用
- 批准号:
10393056 - 财政年份:2021
- 资助金额:
$ 188.67万 - 项目类别:
Inflammasome and Gasdermin Signaling Networks for Regulation of Pyroptosis and Cytokine Release
用于调节焦亡和细胞因子释放的炎性体和 Gasdermin 信号网络
- 批准号:
10441352 - 财政年份:2020
- 资助金额:
$ 188.67万 - 项目类别:
Inflammasome and Gasdermin Signaling Networks for Regulation of Pyroptosis and Cytokine Release
用于调节焦亡和细胞因子释放的炎性体和 Gasdermin 信号网络
- 批准号:
10024450 - 财政年份:2020
- 资助金额:
$ 188.67万 - 项目类别:
Inflammasome and Gasdermin Signaling Networks for Regulation of Pyroptosis and Cytokine Release
用于调节焦亡和细胞因子释放的炎性体和 Gasdermin 信号网络
- 批准号:
10223154 - 财政年份:2020
- 资助金额:
$ 188.67万 - 项目类别:
Alternative pathways of gasdermin function and IL-1beta secretion in granulocytic leukocytes
粒细胞白细胞中 Gasdermin 功能和 IL-1β 分泌的替代途径
- 批准号:
10024453 - 财政年份:2020
- 资助金额:
$ 188.67万 - 项目类别:
Alternative pathways of gasdermin function and IL-1beta secretion in granulocytic leukocytes
粒细胞白细胞中 Gasdermin 功能和 IL-1β 分泌的替代途径
- 批准号:
10654570 - 财政年份:2020
- 资助金额:
$ 188.67万 - 项目类别:
Alternative pathways of gasdermin function and IL-1beta secretion in granulocytic leukocytes
粒细胞白细胞中 Gasdermin 功能和 IL-1β 分泌的替代途径
- 批准号:
10223157 - 财政年份:2020
- 资助金额:
$ 188.67万 - 项目类别: